The document discusses various approaches to designing implantable drug delivery systems. It describes systems that use diffusion processes like polymer membrane permeation or matrix diffusion to control drug release. It also covers systems that use activation processes like osmotic pressure, vapor pressure, hydration or hydrolysis to control drug release. Finally, it mentions systems that use feedback regulated mechanisms, where drug release is activated and controlled by the concentration of biochemical substances detected at the implant site.

1. Prepared by:
N.LAKSHMI PRIYA

2. List of contents
 Effect of physicochemical properties on parenteral absorption
 Introduction
Approaches to design implantable drug delivery systems
(a) Controlled drug delivery by diffusion process
 Polymer membrane permeation- controlled drug delivery
 Matrix diffusion-controlled drug delivery
 Microreservior partition-controlled drug delivery system
 Membrane matrix hybrid-type drug delivery system
(b) Controlled drug delivery by activation process
 Osmotic pressure
 Vapor pressure
 Magnetically
 Hydration
 Hydrolysis
(c) Controlled drug delivery by feed back regulated mechanism
 Bioerosion
 Bioresponce
REFRENCES

3. Effect of Physicochemical Properties on
Parenteral Absorption
Drug particle in suspension
Dissolution
Drug solutes in solution
Partitioning
Drug solution in tissue
fluid
Absorption
Systematic circulation
Target tissue Elimination

4.  Rate of dissolution of solid in formulation vehicle
 Particle size and crystal habit
 pH of the formulation
 pKa of drug
 Lipophillicity of the drug
 Tissue fluid/vehicle partition coefficient
 Solubility of drug at biological fluid at injection site
 Presence of other ingredients in the formulation and their
interaction with the drug molecule

5. Implantable drug delivery system
an introduction
 Implantable drug delivery systems are placed completely under the
skin — usually in a convenient but inconspicuous(not clear) location.
The patient is aware of only a small bump under the skin.
 designed to transmit drugs and fluids into the bloodstream without
the repeated insertion of needles.
 well suited to the drug delivery requirements of insulin, steroids,
chemotherapeutics, antibiotics, analgesics, total parenteral nutrition,
and heparin
 There is little chance of infection or interference with daily activities
Because the device is completely subcutaneous, with no opening in
the skin

6.  In 1861 Lafarge pioneered the concept of IDDS for long term
continuous administration of crystalline hormone in the form of
solid steroid pellet
 But the release profile was not constant and can not be readily
controlled in terms of precision of the release rate and duration
of action
 While it is possible to surgically implant and remove drug-
concentrative devices or polymeric matrices, the requirement
for such intervention could have a significant negative impact on
the acceptability
 Two approaches to this problem seem possible
1. Use of implanted electrically driven pumps
2. Use of erodible implants
Approaches to the development of
Implantable drug delivery system

7.  Number of approaches have been developed to achive
controlled administration of drugs via implantation
(1) Controlled drug delivery by diffusion (paravum )process
 Diffusion of the drug out of the device or solvent into the
polymer ultimately contributes to the drug-release process
 Release of the drug from the device is preprogrammed at a
specific rate profile
 This is accomplished by a system design which controls
molecular diffusion of drug in or and/or across barrier
medium surrounding the system
 This systems can be further sub classified in to number of
classes

8. (A) Polymer membrane permeation- controlled
drug delivery using
1. Non porous membrane
2. Micro porous membrane
3. Semi permeable membrane
 Here the drug formulation is totally or partially encapsulated
within a drug reservoir compartment and the drug release
surface is covered by a rate limiting polymeric membrane
having a specific permeability for drug
drug reservoir
polymeric membrane
Drug contained in a
formulation

9. •The dug reservoir can exist in to a solid , suspension or in a
solution form and polymeric membrane fabricated in the
form of non porous{homogenous or heterogeneous}, micro
porous or semipermiable membrane.
•Encapsulation of drug formulation in to the reservoir
compartment can be done by
1. Injection molding
2. Spray coating
3. microencapsulation
Different shapes of the systems like sphere , cylinder or
sheet can be fabricated
• An example of this type of implantable drug delivery
system is A NORPLANT SUBDERMAL IMPLANT and
OCUSERT SYSTEM

10. (b) Polymer Matrix diffusion-controlled drug
delivery
 In this type of preplanned drug delivery system the drug
reservoir is prepared by homogenous dispersion of drug
particles in a rate controlling polymer matrix fabricated from
either a lipophillic or a hydrophilic polymer
 The drug dispersion in a polymer matrix is done by
1. Blending finely divided drug particles with a liquid polymer or
a viscous base followed by cross linking of the polymer chain
2. Mixing the drug with a polymer at an elevated temperature
3. Dissolving drug and polymer in a common solvent followe by
solvent evaporation at elevated temperature or under vacuum
 The resultant drug polymer dispersion is then molded or
extruded to form a drug delivery devices of various shapes
 Example is a nitro-dur TDDS

11. Drug release
Drug release
Drug depleted zone
Gel layer
Drug
reservoir{dispersion}
Lipophillic polymer
Non swollable matrix
Hydrophilic polymer
Swollable matrix

12. (C) Microreservior partition-controlled drug
delivery system
 In this type drug reservoir is fabricated by micro
dispersion of aqueous suspension of a drug using a high
energy dispersion technique in to a biocompatible
polymer such as silicone elastomer to form a
homogenous dispersion of many discrete , unreachable
microscopic drug reservoir
 Depending on the physicochemical properties of the
drug and the desired rate of drug release , the device can
be further coated with polymer to modify mechanism
and rate of release
 example is the transdermal nitro disc system

13. Polymer matrix
Microscopic Drug
reservoir
{liquid compartment}
Coating membrane
Polymer -solution interface

14. (d) Membrane matrix hybrid-type drug delivery
system
 This device is a hybrid of Polymer Matrix diffusion-controlled
drug delivery and Polymer membrane permeation- controlled
drug delivery system aim is to take advantage of controlled
release kinetic offered by Polymer membrane permeation-
controlled drug delivery system and to avoid risk of dose
dumping from reservoir compartment of this type of drug
delivery system
 Drug reservoir is formed by dispersion of drug in to a polymer
matrix which is further coated by a semi permeable polymeric
membrane
 Example is a norplant II sub dermal system

15. (II) Controlled drug delivery by
activation process
 In this type release of the drug is activated by some
physical , chemical, or biological process and/or by the
energy supplied externally and the rate of release is than
regulated by the processes applied or input of energy
 Based on the processed applied these activation modulated
drug delivery system can be classified in to
1. Osmotic pressure activated
2. Vapor pressure activated
3. Magnetically activated
4. Hydrolytic-activated
5. Hydration activated

16. Osmotic pressure activated drug delivery system
 In this type of controlled drug delivery system the release
of the drug takes place due to osmotic pressure
 Drug reservoir which can be either a solid or a suspension
is contained in a semipermiable housing
 The release is activated through a specially formed orifice
and rate of release is modulated by controlling the osmotic
gradient
 Thus release rate is dependent on water permeability of
membrane, solubility of osmogen, effective surface area of
semipermiable housing as well as osmotic gradient
 Representatative example of this type of implantable
controlled release drug delivery system is alzet osmotic
pump

17. Alzet osmotic pump

18. Vapor pressure activated implantable drug
delivery system
 The drug reservoir which ids a solution formulation is
contained in to an infusate chamber
 By freely movable bellow the chamber is a pumping
system physically separated from the vapors pressure
chamber which contains vaporizable fluids such as a
fluorocarbon
 The fluorocarbon vaporizes at body temperature
creating a vapor pressure that pushes bellow to move
upward and forces the drug solution to get delivered

19. Magnetically activated implantable drug delivery
system
•A magnetic wave triggered
mechanism is incorporated in
to drug delivery device and
drug can be triggered to be
released at varying rate
depending on the magnitude
and duration of the
electromagnetic energy
applied
Magnetic ring
Coated
polymer
Magnet inside polymer matrix

20. Hydration activated drug delivery system
 This system depends on the hydration induced
swelling process by tissue fluid at implantable site to
activate drug release
 In this system drug reservoir is dispersed in to
swollable polymer matrix fabricated from hydrophilic
polymer that become swollen upon hydration
 Drug is released from microscopic water filled pore
channels in to the polymer matrix and
 Release rate of drug is controlled by swelling of the
polymer matrix

21. Hydrolysis activated drug delivery system
 Release of drug is activated by hydrolysis of a bioerodable
polymer by the cell fluid at the implantation site
 Biodegradable polymer like
1. Co(lactic-glycolic)polymer
2. Poly(orthoester)
3. Poly(anhydride) are used in fabrication of this type of
implantable drug delivery system
This system is made by dispersing loading dose of a drug
with a biodegradable polymer , which is then molded in
to pellet or a bead shaped implant
Example is a LHRH{goserelin} releasing biodegradable sub
dermal implant

22. (c) Controlled drug delivery by feed back
regulated mechanism
 using this group of controlled drug delivery system the
release of a drug is activated by some biochemical
molecule in the body and its concentration at the
implantable site via feedback mechanism
 And the rate of controlled release of drug is regulated
by the concentration of biochemical substance
detected by a sensor in the feedback mechanism

23. Bioerosion regulated drug delivery system
 This system consist of a drug dispersed in to a
biodegradable polymer matrix like poly vinyl methyl ether
and is coated with immobilized urease in a neutral pH.in
the presence of urea urease at the surface of drug delivery
system metabolize urea to form ammonia causing increase
in pH at which polymer degrades leading to drug release
U
U
U
U U
U
U
U
U U UU
U
U
U
Hydrocortisone Urea
Ammonia
Urease
Alkaline pH
Polymer
Erosion
Hydrocortisone release

24. Bioresponce activated drug delivery system
 Drug reservoir is contained in a device enclosed by a
bioresponsive polymer membrane whose permeability is
controlled by conc. of a biochemical agent contained where the
system is located
 Example is a glucose triggered insulin delivery system in which
insulin reservoir is capsulated within hydrogel membrane having
amineNR2 groups
 In alkaline pH NR2 is neutral and membrane is unsellable and
impermeable to insulin
 As glucose, triggering agent penetrates in to membrane it is
oxidized to glucuronic acid by enzyme glucose oxidise contained
in a membrane
 NR2 groups are protonated and hydro gel membrane becomes
swollable and permeable for insulin.
 Amt of release is dependant on the concentration of glucose
entering in to membrane

25. REFRENCES
1. NOVEL DRUG DELIVERY SYSTEM, Yie. W
Chien, second edition, marcel dekker inc,
page 381
2. DRUG DELIVERY SYSTEMS, Vasant V.
Ranade Mannfred A. Hollinger Second
Edition,